Process for the oxidation of aldoses



. Patented Nov. 8, 1927.

UNITED STATES PATENT OFFICE.

ARTHUR STOLL, OF ARLESHEIM, NEAR BASEL, AND WALTER KUSSlYIAUL, 0E BASEL, SWITZERLAND, ASSIGNORS TO THE FIRM CHEMICAL WORKS FORMERLY SANDOZ, OF

BASEL, SWITZERLAND.

PROCESS FOR THE OXIDATION OF ALDOSES.

No Drawing. Application filed May 16, 1927, Serial No. 191,922, and in Germany June 12, 1925.

The oxidation of aldoses, e. g. glucose, to the respective monocarboxylic acids with hypobromite or hypoiodite is known and can be performed so exactly that it was possible to work out a dosage of sugars making use of this princi le (see Willstatter and Schudel, Berichte er deutschen chemischen -Gesellschaft 51, 780, 1918). Further, Honig and Tempus (loc. cit. 57 ,7 89, 1924) prepared gluconic acid by oxidizing glucose with barium hypobromite. The reaction can not be so easily performed if hypochlorites are used. Glucose f. i. is in part further degraded, even so far as to form oxalic acid and carbonic acid. (Brautigam, Pharm. Ztg. 5. .6, 636 and Chem. Zentralblatt 1901, II, 680), whilst the gluconic acid has up to now not yet been iso oxidation with hypochloritesproceeds through gluconic acid. It has even been scribed (Journ. Soc. Chem. Ind. 41, p. 2829,

1922) which consists in the addition of equivalent of calcium bromide when oxidizing the sugars with chlorine. The hypochloric acid which is set free in this process is from time to time neutralized with calcium carbonate. A few hours are necessary at the very least for this process and it can only be performed in an apparatus resistant to hydrochloric acid. Moreover at the high temperature used, considerable quantities of bromine set 'free from the calcium bromide by chlorine escape, and this can certainly be considered as a serious disadvantage for industrial purposes. The new process is much cheaper than that of the literature as cited, because it necessitates at most one quarter of the quantity of bromine otherwise used.

A process has now been found according to ated from the products ofreaction. According to our own trials, the

may be used with the same efiect as 'The presence of bromine or iodine influences this reaction otherwise so destructive, in such a manner that the oxidation sto s at the monocarboxylic acid, viz. all of t e aldose can be transformed into the monocarboxylic acid before the oxidation process advances. Under these conditions the yields are as good as if hypobromite or hypoiodite would have been used as oxidizing agent and this is the case with all aldoses coming into con sideration, such' as for example glucose, galactose, mannose, lactose and maltose. The new process possesses also the advan-. tage' that it is carried out in an alkaline medium, which does not affect the material of the apparatus and from which no bromine escapes, whilst in the known process, on account of an acid medium, corrosion of the apparatus and escape of bromine take place.

The quantity of bromine or iodine to be added, e. g. in the form of their soluble salts may be less than of an equivalent of the amount of hypochlorite necessary for the oxidation. Alkali, alkali earth or ma esia ases. Further, the process may be performed in a variety of ways. For instance, it is quite indifferent whether a definite hypochlorite solution is added to a solution of sugar containing bromine or iodine or whether chlorine gas is introduced into a mixture of alkali with a salt of hydrobromic or hydroiodic acid and the sugar. It is important for a good reaction, that the process be performed at a low temperature. The isolation of the monocarboxylic acids is carried out in a known manner.

The following examples illustrate the new process.

Ewample 1.

An oxidizing solution is prepared by introducing at a low temperature 24.3 g. of chlorine in 590 com. of a 10% caustic potash lye. This solution is then added small oxidation portions to a well-cooled solution of 60 g. of glucose and 8 g. of sodium bromide in 250 ccm. of water. It is advantageous to add the last portions more slowly. The reaction is finished when iodide starch paper remains unaltered. The mass is then concentrated to a sirupy consistency, without re ard to the precipltation of potassium choride that takes place. The gluconic acid is then liberated by acidulating with hydrochloric acid until Congo paper turns to a steel blue, the crystals of potassium chloride are filtered ofi and the acid is neutralized with milk of adding 78 g. of sodium sulphate.

lime. After some hours the mass becomes solid and the gluconate of calcium is filtered ofi. Raw roduct 62 g. The product can be purifie by recrystallization from hot water; on incmeration it leaves 13.51% of CaO 0,2183 g. gave 0,0295 g. (1210), calculate' for (C,H,,O,) Ca=13,03%CaO.

Ewample I 2.

A solution of 60 g. of glucose in 250 ccm. ofwater is mixed with milk of lime obtained from 30,8 g. of lime; then 3,5 g. of sodium bromide are added. Into this mixture 24,5 g. of chlorine gas are introduced while cooling and agitating. As soon as the oxidation begins, the temperature rlses. By cooling and regulating of the chlorine the temperature should be kept below 15 C. -When iodide starch paper indicates that the whole of the oxidizing agent has been spent, the lime is precipitated by The raw solution of sodium gluconate is then 0011'- centrated, the gluconic acid liberated from 1 its sodium salt and concentrated to a sirupy consistency. The greater amount of the common salt precipitates and is eliminated by filtering oil or hydro-extracting. The concentrated solution of gluconic acid is worked up as indicated in Example 1.

Ewample 3.

11,5 g. of magnesia usta are hydratized with 200 ccm. of water by heating them for three hours on the waterbath. Then 2,6 g. of bromine are added to 20 ccm. of this paste whilst cooling. The reaction product thus obtained is then added to a well-cooled solution of 30 g. of glucose in 120 com. of water. The rest of the magnesium hydroxide paste is treated with 10,7 g. of chloride gas and the solution thus obtained is'added slowly and under cooling to the sugar solution. After the oxidizing agent is s ent, the solution is concentrated in vacuo an the resulting syrup ca. 60'ccm.) is mixed under stirring with 1 liter of alcohol (95% The ma esium salt separates and solidi es over nig t forming a. crystalline de osit. It is filtered off, washed with alcoho and ether,

to furnish 22,7 g. The product may be reobtained (0,2412 g. gave 0,0323

Example. 4. I

30 g. of galactose are dissolved in 100 com. of water, then a solution of 2,6 g. of bromine in 15 ccm. of milk of lime (from 1,5 g. of CaO) is added to the well cooled mixture. The oxidation is then carefully performed as in the preceding examples with a solution of hypochlorite obtained from 135 com. of milk of lime (from 13,5 g. of CaO) and 11 of chlorine. After the oxidation is finishe the solution is concentrated to 80 com. On cooling, a part separates out and can be filtered off. A further quantity is obtained by adding alcohol to the filtrate. Yield: 29,,1 g. of the ,recrys tallized salt. The salt loses 14,9% of its weight in a high vacuo at 100 C. (2 molecules). On incineration 13,39% of GaO are g. of CaO). (C,H,,O.,) ,Ca:13,03% of Example 5.

To a solution of 180 g. of lactose in 1 liter of water, a solution of 6,3 g. of iodine in 23 com. of a milk of lime containing 2,3 g. of 0210 is added. The oxidation started by this small quantity of hypoiodite, is then continued by a hypochlorite solution formed by introducing 33,8 g. of chlorine into 440 com. of milk of lime containing 44 g. of 021.0. The only feebly muddy solution is then concentrated and the roduct of oxidation precipitated with alco ol. Dissolved in hot water, the salt separates on addition of alcohol in form of fine, clear crystals combined to crusts. Yield: 146 g. The salt has been proved to be a double salt of lactobionate calcium and chloride of calcium. The crystals lose their water of crystallization very slowly even in a high vacuo at Calculated for 09.0)

of the galactonate of calcium 100-105. C. After 20 hours of dryingthe to the respective monocarboxylic acids, consisting in treating aldoses in an alkalinesosisting in treating aldoses in an alkaline solulution with hypochlorites in the presence of tion with hypochlorites in the presence of a Y a salt of bromlne. 1 salt of a halogen of higher molecular weight In witness whereof we have hereunto 5 than chlorine. signed our names this 4th day of May 1927.

2. A process for the oxidation of aldoses ARTHUR STOLL- to the respective monocarboxylic acids, con- WALTER KUSSMUL. 

